Myoinositol 1-phosphatase, a pivotal enzyme in receptor-mediated Ca2+ mobilization, was first described in this laboratory. During the course of purification of the enzyme we have shown that it is distinct from non-specific alkaline phosphatase by its narrow pH optimum (7-8), inhibition by Li+, inertness toward levamisole, heat stability, and greater mobility on polyacrylamide gel electrophoresis. The function of the enzyme is the release of free myoinositol from enantiomeric myoinositol 1-phosphates from two sources: (1) isomerization of glucose 6-phosphate produces the L isomer in a de novo pathway that maintains in the organism the supply of free myoinositol for its primary role, the formation of phosphatidylinositol and its phosphates, and (2) receptor-mediated decomposition of phosphatidylinositol 4,5-bisphosphate releases D-myoinositol, 1,4,5-trisphosphate and diacylglycerol, both recognized as second messengers in Ca2+ mobilization; the trisphosphate is then sequentially dephosphorylated to free myoinositol via D-myoinositol 1,4-bisphosphate and D-myoinositol 1-phosphate, a substrate for the enzyme under investigation. Free myoinositol from both sources is then recycled for renewed receptor activation. The purification of myoinositol 1-phosphatase to homogeneity is the immediate goal of this research necessary to explain three unusual features of the enzyme: (1) its specificity for myoinositol phosphates, its optical non-specificity, and its specific inhibition by Li+. The enzyme isolated from rat testis cytosol has been purified about 300-fold by a series of chromatographic steps including ion exchange and gel filtration HPLC and is nearly homogeneous. Accumulating evidence linking Li+ inhibition of this enzyme to the pharmacological role of Li+ in brain disorders has led to the suggestion that toxic side effects of the drug are due to 6Li and that pure 7Li be used therapeutically. Determination in this laboratory of Li+ toxicity in mice failed to show any difference either in the lethality of the two isotopes or in the inhibition of myoinositol 1-phosphatase. The recommendation for this costly change in Li+ therapy is unjustified.